Variant rs7623685 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001388419.1(KALRN):c.4101+570A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,072 control chromosomes in the GnomAD database, including 13,636 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.41 ( 13636 hom., cov: 32)

Consequence

KALRN
NM_001388419.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.156

Variant links:

Genes affected

KALRN (HGNC:4814): (kalirin RhoGEF kinase) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with the huntingtin-associated protein 1, which is a huntingtin binding protein that may function in vesicle trafficking. [provided by RefSeq, Apr 2016]

KALRN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KALRN	NM_001388419.1 linkuse as main transcript	c.4101+570A>C		intron_variant		ENST00000682506.1	NP_001375348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KALRN	ENST00000682506.1 linkuse as main transcript	c.4101+570A>C		intron_variant			NM_001388419.1	ENSP00000508359	A2

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62845

AN:

151952

Hom.:

13629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.655

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.596

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.586

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.446

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.413

AC:

62862

AN:

152072

Hom.:

13636

Cov.:

AF XY:

0.407

AC XY:

30264

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.369

Gnomad4 ASJ

AF:

0.596

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.452

Gnomad4 FIN

AF:

0.389

Gnomad4 NFE

AF:

0.482

Gnomad4 OTH

AF:

0.441

Alfa

AF:

0.472

Hom.:

35508

Bravo

AF:

0.408

Asia WGS

AF:

0.314

AC:

1092

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.0

DANN

Benign

0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over